ICTV Virus Taxonomy Profile: Paramyxoviridae Rima, Bert; Balkema-Buschmann, Anne; Dundon, William G ...
Journal of general virology,
12/2019, Letnik:
100, Številka:
12
Journal Article
Recenzirano
Odprti dostop
The family
consists of large enveloped RNA viruses infecting mammals, birds, reptiles and fish. Many paramyxoviruses are host-specific and several, such as measles virus, mumps virus, Nipah virus, ...Hendra virus and several parainfluenza viruses, are pathogenic for humans. The transmission of paramyxoviruses is horizontal, mainly through airborne routes; no vectors are known. This is a summary of the current International Committee on Taxonomy of Viruses (ICTV) Report on the family
. which is available at ictv.global/report/paramyxoviridae.
Abstract A population of compact object binaries emitting gravitational waves that are not individually resolvable will form a stochastic gravitational-wave signal. While the expected spectrum over ...population realizations is well known from Phinney, its higher-order moments have not been fully studied before or computed in the case of arbitrary binary evolution. We calculate analytic scaling relationships as a function of gravitational-wave frequency for the statistical variance, skewness, and kurtosis of a stochastic gravitational-wave signal over population realizations due to finite source effects. If the time derivative of the binary orbital frequency can be expressed as a power law in frequency, we find that these moment quantities also take the form of power-law relationships. We also develop a numerical population synthesis framework against which we compare our analytic results, finding excellent agreement. These new scaling relationships provide physical context to understanding spectral fluctuations in a gravitational-wave background signal and may provide additional information that can aid in explaining the origin of the nanohertz-frequency signal observed by pulsar timing array campaigns.
Genetic association studies have identified 215 risk loci for inflammatory bowel disease, thereby uncovering fundamental aspects of its molecular biology. We performed a genome-wide association study ...of 25,305 individuals and conducted a meta-analysis with published summary statistics, yielding a total sample size of 59,957 subjects. We identified 25 new susceptibility loci, 3 of which contain integrin genes that encode proteins in pathways that have been identified as important therapeutic targets in inflammatory bowel disease. The associated variants are correlated with expression changes in response to immune stimulus at two of these genes (ITGA4 and ITGB8) and at previously implicated loci (ITGAL and ICAM1). In all four cases, the expression-increasing allele also increases disease risk. We also identified likely causal missense variants in a gene implicated in primary immune deficiency, PLCG2, and a negative regulator of inflammation, SLAMF8. Our results demonstrate that new associations at common variants continue to identify genes relevant to therapeutic target identification and prioritization.
To further resolve the genetic architecture of the inflammatory bowel diseases ulcerative colitis and Crohn's disease, we sequenced the whole genomes of 4,280 patients at low coverage and compared ...them to 3,652 previously sequenced population controls across 73.5 million variants. We then imputed from these sequences into new and existing genome-wide association study cohorts and tested for association at ∼12 million variants in a total of 16,432 cases and 18,843 controls. We discovered a 0.6% frequency missense variant in ADCY7 that doubles the risk of ulcerative colitis. Despite good statistical power, we did not identify any other new low-frequency risk variants and found that such variants explained little heritability. We detected a burden of very rare, damaging missense variants in known Crohn's disease risk genes, suggesting that more comprehensive sequencing studies will continue to improve understanding of the biology of complex diseases.
To compare the efficacy of whole genome sequencing (WGS) with targeted next-generation sequencing (NGS) in the diagnosis of inherited retinal disease (IRD).
Case series.
A total of 562 patients ...diagnosed with IRD.
We performed a direct comparative analysis of current molecular diagnostics with WGS. We retrospectively reviewed the findings from a diagnostic NGS DNA test for 562 patients with IRD. A subset of 46 of 562 patients (encompassing potential clinical outcomes of diagnostic analysis) also underwent WGS, and we compared mutation detection rates and molecular diagnostic yields. In addition, we compared the sensitivity and specificity of the 2 techniques to identify known single nucleotide variants (SNVs) using 6 control samples with publically available genotype data.
Diagnostic yield of genomic testing.
Across known disease-causing genes, targeted NGS and WGS achieved similar levels of sensitivity and specificity for SNV detection. However, WGS also identified 14 clinically relevant genetic variants through WGS that had not been identified by NGS diagnostic testing for the 46 individuals with IRD. These variants included large deletions and variants in noncoding regions of the genome. Identification of these variants confirmed a molecular diagnosis of IRD for 11 of the 33 individuals referred for WGS who had not obtained a molecular diagnosis through targeted NGS testing. Weighted estimates, accounting for population structure, suggest that WGS methods could result in an overall 29% (95% confidence interval, 15–45) uplift in diagnostic yield.
We show that WGS methods can detect disease-causing genetic variants missed by current NGS diagnostic methodologies for IRD and thereby demonstrate the clinical utility and additional value of WGS.
Although a common cause of disease, copy number variants (CNVs) have not routinely been identified from next-generation sequencing (NGS) data in a clinical context. This study aimed to examine the ...sensitivity and specificity of a widely used software package, ExomeDepth, to identify CNVs from targeted NGS data sets. We benchmarked the accuracy of CNV detection using ExomeDepth v1.1.6 applied to targeted NGS data sets by comparison to CNV events detected through whole-genome sequencing for 25 individuals and determined the sensitivity and specificity of ExomeDepth applied to these targeted NGS data sets to be 100% and 99.8%, respectively. To define quality assurance metrics for CNV surveillance through ExomeDepth, we undertook simulation of single-exon (n=1000) and multiple-exon heterozygous deletion events (n=1749), determining a sensitivity of 97% (n=2749). We identified that the extent of sequencing coverage, the inter- and intra-sample variability in the depth of sequencing coverage and the composition of analysis regions are all important determinants of successful CNV surveillance through ExomeDepth. We then applied these quality assurance metrics during CNV surveillance for 140 individuals across 12 distinct clinical areas, encompassing over 500 potential rare disease diagnoses. All 140 individuals lacked molecular diagnoses after routine clinical NGS testing, and by application of ExomeDepth, we identified 17 CNVs contributing to the cause of a Mendelian disorder. Our findings support the integration of CNV detection using ExomeDepth v1.1.6 with routine targeted NGS diagnostic services for Mendelian disorders. Implementation of this strategy increases diagnostic yields and enhances clinical care.
A plasma gas bubble‐in‐liquid method for high production of selectable reactive species using a nanosecond pulse generator has been developed. The gas of choice is fed through a hollow needle in a ...point‐to‐plate bubble discharge, enabling improved selection of reactive species. The increased interface reactions, between the gas‐plasma and water through bubbles, give higher productivity. H2O2 was the predominant species produced using Ar plasma, while predominantly NO3− and NO2 were generated using air plasma, in good agreement with the observed emission spectra. This method has nearly 100% selectivity for H2O2, with seven times higher production, and 92% selectivity for NO3−, with nearly twice the production, compared with a plasma above the water.
A plasma gas bubble‐in‐liquid, with chosen gas, method is described. The gas of choice enables improved selection of reactive species and increased interface reactions enable higher productivity. “Ar” plasma produces a high concentration of H2O2, while “air” plasma produces high concentrations ofNO3− and NO2. The selectivity and productivity are much higher than with a plasma created above liquid.
The primary objective of the preclinical dental anatomy course in the predoctoral dental curriculum is to introduce students to cognitive and psychomotor skills related to the morphology and spatial ...and functional relationships of human dentition. Traditionally, didactic content for the subject is found in textbooks and course manuals and summarized by the faculty in lectures to the entire class. Psychomotor skills associated with recognition and reproduction of tooth morphology are traditionally learned by examining preserved tooth specimens and their cross‐sections, combined with producing two‐dimensional line drawings and carving teeth from wax blocks. These activities have little direct clinical application. In most cases, students are passive in the learning process, and assessment of student performance is unilateral and subjective. A recently revised dental anatomy module at the University of Illinois at Chicago College of Dentistry integrates independent class preparation with active small‐group discussion and patient scenario‐based wax‐up exercises to replace missing tooth structure on manikin teeth. The goal of the revision is to shift emphasis away from decontextualized technical learning toward more active and clinically applicable learning that improves conceptual understanding while contributing to early acquisition of psychomotor skills. This article describes the rationale, components, and advantages of the revised module and presents a pre‐post comparison of student learning outcomes for three class cohorts (N=203).
Abstract
We report multiple lines of evidence for a stochastic signal that is correlated among 67 pulsars from the 15 yr pulsar timing data set collected by the North American Nanohertz Observatory ...for Gravitational Waves. The correlations follow the Hellings–Downs pattern expected for a stochastic gravitational-wave background. The presence of such a gravitational-wave background with a power-law spectrum is favored over a model with only independent pulsar noises with a Bayes factor in excess of 10
14
, and this same model is favored over an uncorrelated common power-law spectrum model with Bayes factors of 200–1000, depending on spectral modeling choices. We have built a statistical background distribution for the latter Bayes factors using a method that removes interpulsar correlations from our data set, finding
p
= 10
−3
(≈3
σ
) for the observed Bayes factors in the null no-correlation scenario. A frequentist test statistic built directly as a weighted sum of interpulsar correlations yields
p
= 5 × 10
−5
to 1.9 × 10
−4
(≈3.5
σ
–4
σ
). Assuming a fiducial
f
−2/3
characteristic strain spectrum, as appropriate for an ensemble of binary supermassive black hole inspirals, the strain amplitude is
2.4
−
0.6
+
0.7
×
10
−
15
(median + 90% credible interval) at a reference frequency of 1 yr
−1
. The inferred gravitational-wave background amplitude and spectrum are consistent with astrophysical expectations for a signal from a population of supermassive black hole binaries, although more exotic cosmological and astrophysical sources cannot be excluded. The observation of Hellings–Downs correlations points to the gravitational-wave origin of this signal.
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